Emetic liability testing in ferrets.

Evidence of a candidate drug's efficacy and safety is mandatory for successful drug registration by regulatory authorities. However, a third property, tolerability, often determines a drug's acceptance by the patient population. Gastrointestinal events often determine the maximum tolerated dose in Phase I clinical trials. If the plasma concentrations achieved at the maximum tolerable dose are below those required for efficacy, the drug will certainly fail. The identification of a compound's emetic/nauseogenic liability early in the discovery process can be critical to the ultimate success of the drug discovery project. Ferrets are small carnivores (~1 kg) of the Mustelidae family that vomit in response to many pharmacological classes of drugs as well as to cytotoxic chemotherapeutics and radiation. This unit describes a simple method for evaluating the emetic and nauseogenic potential of drug candidates in ferrets.